Hypersensitivity pneumonitis (HP) is one of those Step 1 “pattern recognition” diseases: a restrictive/interstitial lung disease caused by repeated inhalation of an antigen, leading to immune-mediated inflammation of the alveoli and small airways. The test loves it because it blends immunology (Type III/IV hypersensitivity) with pulmonology (restrictive PFTs + decreased DLCO) and a classic occupational/environmental exposure story.
Where it fits (big picture)
HP is an interstitial lung disease (ILD) that primarily affects:
- Alveoli
- Terminal bronchioles
- Interstitial tissue
It can present as acute, subacute, or chronic disease—often depending on intensity and duration of exposure.
Step clue: Restrictive symptoms + exposure history + imaging showing ground-glass or centrilobular nodules (early) or fibrosis (late) = think HP.
Definition (what it is)
Hypersensitivity pneumonitis is an immune-mediated lung disease caused by inhaled organic antigens (or certain chemicals) that trigger:
- Immune complex–mediated inflammation (Type III) and
- T-cell–mediated delayed hypersensitivity (Type IV)
This leads to alveolitis, small airway inflammation, and in chronic cases, fibrosis.
First Aid cross-reference: Commonly appears under Interstitial lung diseases and Hypersensitivity pneumonitis (often alongside pneumoconioses, sarcoidosis, idiopathic pulmonary fibrosis).
High-yield exposures (know these cold)
Classic antigen sources
| Nickname / Setting | Common Antigen Source | High-yield clue |
|---|---|---|
| Farmer’s lung | Moldy hay (thermophilic actinomycetes) | Fevers/cough after handling hay |
| Bird fancier’s lung | Bird droppings/feathers (avian proteins) | Pigeon/parakeet exposure |
| Hot tub lung | Mycobacterium avium complex aerosol | Symptoms after hot tub use (immune reaction, not classic infection) |
| Malt worker’s lung | Mold spores from barley | Brewery/malt facility exposure |
| Humidifier/AC lung | Contaminated water reservoirs | Office/home HVAC exposure |
Exam pitfall: HP is from inhaled antigens; eosinophilia/asthma-like atopy points more toward allergic asthma or ABPA, not classic HP.
Pathophysiology (why it happens)
Immunology core
Repeated exposure causes:
- Type III hypersensitivity
- Antigen + IgG → immune complexes
- Complement activation → neutrophilic inflammation
- Type IV hypersensitivity
- Th1-mediated delayed reaction
- Granulomatous inflammation
Tissue-level consequences
- Interstitial inflammation (alveolitis)
- Bronchiolitis (small airways)
- Noncaseating granulomas (often described as “poorly formed”)
- With chronic exposure → fibrosis, architectural distortion, and restrictive physiology
Buzzwords
- “Noncaseating granulomas” (but think: not the same clinical package as sarcoidosis)
- “Lymphocytic alveolitis”
- “Poorly formed granulomas” (a common pathology phrasing for HP)
Clinical presentation (what you see)
Acute HP (hours after exposure)
- Fever, chills
- Dry cough
- Dyspnea
- Chest tightness, malaise
- Symptoms often occur 4–8 hours after exposure and improve with antigen avoidance
Subacute / Chronic HP (weeks to years)
- Progressive exertional dyspnea
- Chronic cough
- Fatigue, weight loss
- End-inspiratory crackles
- In chronic disease: possible clubbing (from fibrosis)
Step-style stem: A bird owner with episodic fevers + cough after cleaning the cage; later develops progressive dyspnea and restrictive lung disease.
Diagnosis (how to lock it in)
HP is a clinic + exposure + imaging diagnosis supported by labs/bronchoscopy, and occasionally biopsy.
1) Pulmonary function tests (PFTs)
- Restrictive pattern
- ↓ TLC
- ↓ FVC (often with normal/↑ FEV1/FVC ratio)
- ↓ DLCO (gas exchange impairment due to interstitial involvement)
2) Imaging
Chest X-ray
- Can be normal early
- Diffuse interstitial pattern in more established disease
High-resolution CT (HRCT)
- Ground-glass opacities (active inflammation)
- Centrilobular nodules
- Mosaic attenuation / air trapping (small airway involvement)
- Chronic: fibrotic changes (reticulation, traction bronchiectasis)
High-yield contrast
- HP often has airway-centered findings (air trapping/mosaic attenuation) because bronchioles are involved.
3) Bronchoalveolar lavage (BAL)
- Lymphocytosis is classic (often CD8-predominant in many teaching schemas)
- Helps distinguish from diseases with more neutrophils/eosinophils depending on context
4) Serology (supportive, not definitive)
- Precipitating IgG antibodies to the offending antigen can be present
- Helpful for exposure confirmation
- Not perfectly specific (exposure ≠ disease)
5) Histology (if needed)
- Interstitial lymphocytic infiltrates
- Poorly formed noncaseating granulomas
- Bronchiolocentric distribution
Treatment (what to do)
Cornerstone: antigen avoidance
- Remove the exposure (birds, moldy hay, contaminated humidifier, etc.)
- Workplace/environment modifications (ventilation, PPE, remediation)
Pharmacologic therapy
- Systemic corticosteroids can help in acute/subacute disease or significant symptoms:
- Reduce inflammation more quickly
- Do not replace avoidance
- Chronic fibrotic HP may respond less dramatically; goal becomes:
- Prevent progression
- Manage hypoxemia and complications
Supportive care (esp. chronic disease)
- Oxygen if hypoxemic
- Pulmonary rehab
- Vaccinations (flu, pneumococcal)
- In advanced end-stage fibrosis: consider transplant evaluation
How to distinguish HP from similar Step diseases
HP vs Asthma
| Feature | Hypersensitivity pneumonitis | Asthma |
|---|---|---|
| Primary site | Alveoli + interstitium + small airways | Bronchi |
| Hypersensitivity type | Type III + Type IV | Mostly Type I (IgE) |
| PFTs | Restrictive, ↓ DLCO | Obstructive, DLCO usually normal/↑ |
| Key clue | Antigen exposure + systemic symptoms (fever) | Atopy, wheeze, triggers |
HP vs Sarcoidosis
| Feature | HP | Sarcoidosis |
|---|---|---|
| Trigger | Inhaled antigen exposure | Idiopathic; systemic granulomatous disease |
| Granulomas | Poorly formed noncaseating | Well-formed noncaseating |
| Imaging clue | Ground-glass, centrilobular nodules, air trapping | Bilateral hilar adenopathy (classic) |
| Systemic findings | Less stereotyped; exposure-driven | Can have erythema nodosum, uveitis, hypercalcemia |
HP vs Idiopathic Pulmonary Fibrosis (IPF)
| Feature | HP | IPF |
|---|---|---|
| Cause | Known antigen exposure | Idiopathic |
| Onset | Acute/subacute episodes possible | Insidious, progressive |
| HRCT | Ground-glass/nodules/air trapping; may fibrose | Subpleural honeycombing, basilar predominance |
| Treatment focus | Avoid antigen ± steroids | Antifibrotics (Step-level: know it’s progressive) |
High-yield associations & “testable one-liners”
- HP is an immune-mediated ILD due to repeated inhalation of antigens.
- Mechanism: Type III (immune complex) + Type IV (T-cell–mediated) hypersensitivity.
- PFTs: restrictive + ↓ DLCO.
- HRCT: ground-glass, centrilobular nodules, mosaic attenuation/air trapping.
- BAL: lymphocytosis.
- Path: poorly formed noncaseating granulomas + interstitial inflammation.
- Treatment: antigen avoidance is #1; corticosteroids can help reduce inflammation, especially early.
Rapid Step 1/2 checkpoint (mini drill)
If the stem says:
- “Bird owner” + episodic fevers/dyspnea a few hours after cleaning cages → HP
- “Moldy hay” + cough/dyspnea → HP
- PFTs show restrictive + ↓ DLCO and CT shows ground-glass + air trapping → HP
- Granulomas but no hilar adenopathy story and a clear exposure → HP > sarcoid
Frequently Asked Questions
Why does hypersensitivity pneumonitis cause restrictive lung disease with decreased DLCO?
Hypersensitivity pneumonitis causes restrictive lung disease with decreased DLCO because repeated inhalation of an antigen triggers immune-mediated inflammation in the alveoli, interstitium, and small airways. Type III and Type IV hypersensitivity reactions produce alveolitis and bronchiolitis, and chronic exposure can lead to fibrosis and architectural distortion. That interstitial involvement limits lung expansion and impairs gas exchange, producing restrictive PFTs and a low DLCO.
What exposures are classically associated with hypersensitivity pneumonitis?
Classic exposures include moldy hay, bird droppings or feathers, hot tub aerosol, mold spores from barley, and contaminated humidifier or air-conditioning water reservoirs. These correspond to high-yield associations such as farmer’s lung, bird fancier’s lung, hot tub lung, malt worker’s lung, and humidifier or AC lung. The common theme is repeated inhalation of organic antigens or certain chemicals that trigger an immune reaction in the lungs.
How do you recognize acute versus chronic hypersensitivity pneumonitis?
Acute hypersensitivity pneumonitis typically presents hours after exposure with fever, chills, dry cough, dyspnea, chest tightness, and malaise, often improving when the antigen is avoided. Chronic or subacute disease develops over weeks to years and causes progressive exertional dyspnea, chronic cough, fatigue, weight loss, and end-inspiratory crackles. In more advanced chronic disease, clubbing can appear because of fibrosis.
What imaging and bronchoscopy findings support hypersensitivity pneumonitis?
Findings that support hypersensitivity pneumonitis include ground-glass opacities, centrilobular nodules, and mosaic attenuation or air trapping on high-resolution CT, with fibrotic changes appearing later in chronic disease. Chest X-ray may be normal early or show a diffuse interstitial pattern later. Bronchoalveolar lavage classically shows lymphocytosis, and this helps support the diagnosis when combined with the right exposure history and clinical picture.
What is the main treatment for hypersensitivity pneumonitis, and when are steroids used?
The main treatment for hypersensitivity pneumonitis is antigen avoidance. Removing exposure to the offending source, such as birds, moldy hay, or contaminated humidifiers, is the cornerstone because ongoing exposure drives the inflammation. Systemic corticosteroids can be used in acute or subacute disease or when symptoms are significant to reduce inflammation more quickly, but they do not replace avoidance. Chronic fibrotic disease may respond less dramatically.